This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our collaboration with Dr. Andrej Sali's group at UCSF reflects ongoing efforts to maximize the structural information obtained from cryo-EM density maps. The latest work focuses on the development of an iterative modeling process that explores alignment space in the context of the cryo-EM density map. In such work, more accurate models can be made and selected for. From these early demonstrations, we have composed a plan to increase model accuracy by more tightly coupling model building in MODELLER to the cryo-EM density maps and extending the modeling constraints to include secondary structure features annotated in the density map. The challenge here is in the integration of multiple types of data as well as in the integration of multiple software packages for structure determination, analysis and modeling.